The physiological actions of prostaglandin (PG)F2xcex1 are mediated through interaction with the prostaglandin F2xcex1 (FP) receptor. This receptor has not previously been isolated or purified. FP-encoding DNA and the amino acid sequence of the FP receptor protein was also not known FP receptors are normally found on a wide variety of cells and tissues including the small intestine, corpus luteum, placenta, ovary, brain, myometrium, lung, kidney, stomach, muscle, eye, uterus and trachea, in humans and other animals. Binding of prostaglandin to the FP receptor protein elicits an increase in intracellular calcium levels. This signal causes the tissues to respond, for example, by muscle contraction and in the eye indirectly causes a reduction in intraocular pressure. Studies on PGF2xcex1 binding sites (FP receptors) have been performed using primarily corpus lutea tissue since PGF2xcex1 is a potent luteolytic agent [Powell et al, 1974 Lancet, 1, pp 1120; Powell et al., 1974, Eur. J. Biochem., 41, pp 103-107]. Functional activities of the FP receptor have been studied using tissue preparations such as rabbit jejunum and the cat, bullock and dog iris sphincter tissues [Dong and Jones, 1982 Br. J. Pharmac., 76, pp 149-155; Welburm and Jones, 1978 Prostaglandins, 15, pp 287]. The above methods for studying FP receptor activities have several disadvantages in that they require tissue preparations containing several different but related receptor populations with different ligand binding properties making absolute potency and selectivity impossible. In addition, tissues contain very low levels of FP receptor and since tissue samples are required, compounds cannot satisfactorily be tested as effectors of the human FP receptor.
A novel prostaglandin receptor protein termed FP has been identified from human cells. A DNA molecule encoding the full length FP protein has been isolated and purified, and the nucleotide sequence has been determined. The FP encoding DNA has been cloned into expression vectors and these expression vectors, when introduced into recombinant host cells, cause the recombinant host cells to express a functional FP receptor protein. The novel FP protein, the FP-encoding DNA, the expression vectors and recombinant host cells expressing recombinant FP are useful in the identification of modulators of FP receptor activity.
A method of identifying FP receptor modulators is also disclosed which utilizes the recombinant FP expressing host cells. Modulators of FP activity are useful for the treatment of prostaglandin-related diseases and for modulating the effects of prostaglandins on the FP receptor.